Summary. Background: The optimal approach for venous thrombosis (VTE) prophylaxis during pregnancy and postpartum in women with an increased risk of VTE is not established. Objectives: To evaluate the effectiveness, represented as the incidence of pregnancy-related VTE, and safety, represented as incidence of postpartum hemorrhage (PPH), of a protocol recommending prophylaxis with low-dose low-molecular-weight heparin (LMWH) in women at intermediate to high risk of VTE. Patients/methods: In this retrospective cohort study, we analyzed 34 women (44 pregnancies) with intermediate risk of VTE who received low-dose LMWH for 6 weeks postpartum and 57 women (82 pregnancies) with high risk of VTE who received low-dose LMWH during pregnancy and for 6 weeks postpartum. Pregnancy-related VTE was defined as VTE during pregnancy or £ 3 months postpartum. PPH was defined as blood loss > 500 mL and severe PPH as blood loss > 1000 mL. Results: The incidence of pregnancy-related VTE was 5.5% (95% CI, 2.4-12.3) despite prophylaxis with low-dose LMWH. All events occurred in women at high risk, with a postpartum incidence of 7.0% (95% CI, 2.9-16.7) and antepartum incidence of 1.8% (95% CI, 0.4-9.2). The risk of PPH was 21.6% (95% CI, 14.3-31.3) and severe PPH 9.1% (95% CI, 4.7-16.9), which was not different in women who started LMWH postpartum and those who used LMWH during pregnancy. Conclusions: Although prophylaxis with low-dose LMWH during pregnancy and postpartum proved to be safe, the risk of pregnancy-related VTE is considerable in women with a high risk of VTE. VTE prophylaxis with lowdose LMWH may not be sufficiently effective in these women.

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Satisfaction with pain relief is higher in women receiving epidural analgesia compared with Remifentanil PCA.

Introduction: The objective of this study was to evaluate the placental characteristics of monochorionic twin pregnancies with selective intrauterine growth restriction (sIUGR) classified according to the Gratacós classification based on umbilical artery Doppler measurements. Methods: All consecutive placentas from monochorionic twin pregnancies with sIUGR, (defined as a birthweight discordance > 25% and/or an estimated fetal weight in one twin <10 th centile) examined at our center between May 2002 and February 2018 were included in the study. Each placenta was injected with colored dye to study the angioarchitecture. Primary outcomes were placental share discordance and diameter of the arterio-arterial anastomoses in relation to the umbilical artery Doppler types of sIUGR (Gratacós classification). Results: Of the 83 sIUGR twins included, 27 were classified as Gratacós type I, 24 as type II and 32 as type III. The median gestational age at delivery was 34.3 weeks for type I, compared to 31.2 weeks and 31.6 weeks for type II and type III respectively. A trend towards a higher placental share discordance in type III sIUGR was observed. The median arterioarterial diameter was 1.7 mm (0.8-2.6) in type I, 1.7 mm (0.8-2.6) in type II and 2.8 (2.0-3.5) mm in type III (p<0.01). Conclusions: Type III sIUGR placentas appear to be characterized by a larger diameter of the arterio-arterial anastomoses in type III and a larger placental share discordance compared to type I and II sIUGR. The insights in the placental architecture of sIUGR placentas may offer new views on the pathophysiology of the disease.

ObjectiveTo assess the incidence of and risk factors for adverse long‐term neurodevelopmental outcome in complicated monochorionic pregnancies treated with selective feticide at our centre between 2000 and 2011.DesignObservational cohort study.SettingNational referral centre for fetal therapy (Leiden University Medical Centre, the Netherlands).PopulationNeurodevelopmental outcome was assessed in 74 long‐term survivors.MethodsChildren, at least 2 years of age, underwent an assessment of neurologic, motor and cognitive development using standardised psychometric tests and the parents completed a behavioural questionnaire.Main outcome measuresA composite outcome termed neurodevelopmental impairment including cerebral palsy (GMFCS II‐V), cognitive and/or motor test score of <70, bilateral blindness or bilateral deafness requiring amplification.ResultsA total of 131 monochorionic pregnancies were treated with selective feticide at the Leiden University Medical Centre. Overall survival rate was 88/131 (67%). Long‐term outcome was assessed in 74/88 (84%). Neurodevelopmental impairment was detected in 5/74 [6.8%, 95% confidence interval (CI), 1.1–12.5] of survivors. Overall adverse outcome, including perinatal mortality or neurodevelopmental impairment was 48/131 (36.6%). In multivariate analysis, parental educational level was associated with cognitive test scores (regression coefficient B 3.9, 95% CI 1.8–6.0). Behavioural problems were reported in 10/69 (14.5%).ConclusionsAdverse long‐term outcome in survivor twins of complicated monochorionic pregnancies treated with selective feticide appears to be more prevalent than in the general population. Cognitive test scores were associated with parental educational level.Tweetable abstractNeurodevelopmental impairment after selective feticide was detected in 5/74 (6.8%, 95% CI 1.1–12.5) of survivors.

Although the results of treatment of Hodgkin's disease (HD) have improved considerably in the last decades, the disease remains fatal in a minority of patients. We have recently shown that numbers of activated cytotoxic T cells (CTLs), present in tumor biopsy specimens, differ considerably among individual HD patients. Because CTLs are the major effector cells in elimination of neoplastic cells, we investigated whether the number of activated CTLs is related to the clinical outcome of the individual patient with HD. Activated CTLs present in tumor biopsy specimens of patients with nodular sclerosis or mixed cellularity HD were identified by immunohistochemistry using an antibody directed against granzyme B (GrB), a major constituent of the cytotoxic granules of activated CTLs and natural killer cells, and an antibody directed against CD8. The presence of a high percentage of GrB+ lymphocytes was found to be an unfavorable prognostic marker. The large majority of GrB+ cells were also CD8+, indicating that these cells are activated CTLs. Prognosis was found to decrease with increasing percentages of GrB+ lymphocytes. Optimal discrimination between patients with good and poor prognosis was obtained when the threshold was set at 15% GrB+ cells; 6 of 10 patients with ≥15% GrB+ lymphocytes died as a result of the disease, as compared with 6 of 70 patients with less than 15% GrB+ lymphocytes (P < .0001). In stage-2 patients, the percentage of GrB+ lymphocytes retained its predictive value in a multivariate analysis including histology, sex, age, erythrocyte sedimentation rate, and the presence of B symptoms as covariables. In addition, patients with ≥15% GrB+ lymphocytes had a shortened progression-free survival time (P = .002). We conclude that a high percentage of activated CTLs present in biopsy material of HD patients is a strong indicator for an unfavorable clinical outcome.

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